Journal
CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
Volume 466, Issue 9, Pages 2052-2059Publisher
SPRINGER
DOI: 10.1007/s11999-008-0328-y
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Funding
- NCI NIH HHS [R01 CA 83132, R01 CA083132] Funding Source: Medline
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Neoplastic cells growing under hypoxic conditions exhibit a more aggressive phenotype by activating a cascade of molecular events partly mediated by hypoxia-inducible transcription factor (HIF-1 alpha) and vascular endothelial growth factor (VEGF). The roles of these markers have been studied previously in several cancer lines. We ascertained the frequency of HIF-1 alpha expression, VEGF expression, the degree of neovascularization, and cell proliferation in osteosarcoma samples. Samples from osteosarcoma patients were assessed for HIF-1 alpha and VEGF protein expression using immunohistochemistry, neovascularization using antibodies for Factor VIII, and cell proliferation using the Ki-67 labeling index. Associations between these parameters and clinical features were examined. HIF-1 alpha staining was positive in 35% of patients and metastases were present in 61% of these HIF-1 alpha-positive patients. VEGF protein expression was detected in 69% of patients, 92% of whom were female. We observed an insignificant trend for a higher frequency of VEGF expression in the high-grade as compared to low-grade osteosarcoma. We observed no association between vascular density and proliferation index and any clinical parameters. We found an association between HIF-1 alpha expression and metastatic disease and between VEGF expression and female gender.
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